Circulatory MicroRNAs (miRNAs) as Biomarkers for Diabetic Retinopathy (DR) and Age-Related Macular Degeneration

Abstract

The present disclosure provides methods that find use in determining a likelihood of having or developing diabetic retinopathy (DR) in a subject. Such methods generally include detection of one or more DR diagnostic microRNAs (miRNAs) as described herein. The detection of one or more (e.g., a combination) of such DR diagnostic miRNAs can be used to determine a likelihood of having or developing DR in a subject. Also provided are wet and dry age-related macular degeneration (AMD) diagnostic miRNAs and methods of using same.

1 . A method of determining a likelihood of having or developing diabetic retinopathy (DR) in a subject, the method comprising:
 determining an amount of at least one DR diagnostic miRNA in a biological sample from the subject;   comparing the amount of the at least one DR diagnostic miRNA with a control amount of the at least one DR diagnostic miRNA; and   generating a report indicating a likelihood of having or developing DR in the subject based on results of said comparing the amount of the at least one DR diagnostic miRNA with the control amount of the at least one DR diagnostic miRNA.   
     
     
         2 . The method according to  claim 1 , wherein the biological sample is aqueous humor, vitreous humor, or plasma. 
     
     
         3 . The method according to  claim 2 , wherein the biological sample is aqueous humor and the at least one DR diagnostic miRNA is selected from the group consisting of: miR-let-7b, miR-let-7d, miR-320c, miR-26a, miR-4488, miR-638, miR-29a, and combinations thereof. 
     
     
         4 . The method according to  claim 2 , wherein the biological sample is vitreous humor and the at least one DR diagnostic miRNA is selected from the group consisting of: miR-let-7a, miR-let-7b, miR-let-7c, miR-let-7d, miR-320a, miR-320b, miR-320c, miR-4488, miR-29a, and combinations thereof. 
     
     
         5 .- 12 . (canceled) 
     
     
         13 . The method according to  claim 1 , comprising obtaining the biological sample from the subject. 
     
     
         14 . The method according to  claim 1 , wherein determining the amount of the at least one DR diagnostic miRNA comprises performing quantitative real-time PCR. 
     
     
         15 . The method according to  claim 14 , wherein the quantitative real-time PCR is multiplexed. 
     
     
         16 . The method according to  claim 1 , wherein the report comprises guidance to a clinician as to a treatment recommendation for the subject based on the likelihood of having or developing DR in the subject. 
     
     
         17 . The method according to  claim 16 , wherein the treatment recommendation is control of blood glucose, blood pressure and/or blood cholesterol. 
     
     
         18 . The method according to  claim 16 , wherein the treatment recommendation is administration of an anti-VEGF antibody. 
     
     
         19 . The method according to  claim 16 , wherein the treatment recommendation is scatter laser treatment. 
     
     
         20 . The method according to  claim 16 , wherein the treatment recommendation is focal laser treatment. 
     
     
         21 . The method according to  claim 1 , comprising inputting the amount of the at least one DR diagnostic miRNA into a computer comprising a processor programmed to perform the comparing step, wherein said inputting generates a result for a report. 
     
     
         22 .- 23 . (canceled) 
     
     
         24 . A method of determining efficacy of a therapy for treatment of diabetic retinopathy (DR) in a subject, the method comprising:
 determining an amount of at least one DR diagnostic miRNA in a biological sample from the subject prior to administration of the therapy;   administering the therapy;   determining an amount of the least one DR diagnostic miRNA in a biological sample from the subject following administration of the therapy;   comparing the amount of the at least one DR diagnostic miRNA in a biological sample prior to administration of the therapy with the amount of the at least one DR diagnostic miRNA in a biological sample following administration of the therapy; and   generating a report indicating efficacy of the therapy based on results of said comparing.   
     
     
         25 .- 52 . (canceled) 
     
     
         53 . A method of determining a likelihood of having or developing dry or wet age-related macular degeneration (AMD) in a subject, the method comprising:
 determining an amount of at least one dry or wet AMD diagnostic miRNA in a biological sample from the subject;   comparing the amount of the at least one dry or wet AMD diagnostic miRNA with a control amount of the at least one dry or wet AMD diagnostic miRNA; and   generating a report indicating a likelihood of having or developing dry or wet AMD in the subject based on results of said comparing the amount of the at least one dry or wet AMD diagnostic miRNA with the control amount of the at least one dry or wet AMD diagnostic miRNA.   
     
     
         54 . The method according to  claim 53 , wherein the biological sample is serum. 
     
     
         55 . (canceled) 
     
     
         56 . The method according to  claim 53 , wherein the at least one dry or wet AMD diagnostic miRNA is at least one wet AMD diagnostic miRNA, and wherein the at least one wet AMD diagnostic miRNA is selected from the group consisting of: miR-10b, miR-1306, miR-136, miR-183-star, miR-296-5p, miR-30c, miR-4258, miR-519d, miR-889, and combinations thereof. 
     
     
         57 . (canceled) 
     
     
         58 . The method according to  claim 53 , wherein the at least one dry or wet AMD diagnostic miRNA is at least one dry AMD diagnostic miRNA, and wherein the at least one dry AMD diagnostic miRNA is selected from the group consisting of: miR-1224-3p, miR-1226, miR-29c, miR-3121, miR-3197, miR-32, miR-363-star, miR-639, miR-661, miR-708-star, and combinations thereof. 
     
     
         59 . (canceled) 
     
     
         60 . The method according to any one of  claim 53 , wherein determining the amount of the at least one dry or wet AMD diagnostic miRNA comprises performing quantitative real-time PCR. 
     
     
         61 . The method according to  claim 60 , wherein the quantitative real-time PCR is multiplexed. 
     
     
         62 .- 89 . (canceled) 
     
     
         90 . A method of determining a likelihood of having or developing a resistance to anti-VEGF therapy in a subject suffering from age related macular degeneration (AMD), the method comprising:
 determining an amount of at least one anti-VEGF therapy resistance diagnostic miRNA in a biological sample from the subject;   comparing the amount of the at least one anti-VEGF therapy resistance diagnostic miRNA with a control amount of the at least one anti-VEGF therapy resistance diagnostic miRNA; and   generating a report indicating a likelihood of having or developing anti-VEGF therapy resistance in the subject based on results of said comparing the amount of the at least one anti-VEGF therapy resistance diagnostic miRNA with the control amount of the at least one anti-VEGF therapy resistance diagnostic miRNA.   
     
     
         91 .- 106 . (canceled)